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Peer-reviewedCC BY 4.0PLOS One

A Baltic Sea microbiome-derived Type III polyketide synthase produces host-protective alkylresorcinols in E. coli

  • Susana López-Gutiérrez1
  • Laura A. Espinosa-Barrera2
  • Arianna Soto-Hernández3
  • Holber Zuleta-Prada4
  • Celia Bustos-Brito5
  • César S. Cardona-Félix6
  • José Utrilla7
  • Beatriz Velazquez-Cruz8
  • Yair Cárdenas-Conejo9
  • Jesus Alfredo Araujo-León10
  • Victor Aguilar-Hernández11
  • Juan A. Osuna-Castro
3 more authors
  • Baldomero Esquivel
  • Hugo Serrano-Posada
  • Sara Centeno-Leija
11 affiliations
  1. 1Laboratorio de Biología Sintética, Estructural y Molecular, Facultad de Ingeniería Mecánica y Eléctrica, Universidad de Colima, Coquimatlán, Colima, México
  2. 2Unidad de Biología Integrativa, Centro de Investigación Científica de Yucatán, A. C. (CICY), Mérida, Yucatán, México
  3. 3Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México
  4. 4Laboratorio de Productos Naturales, Área de Química, Departamento de Preparatoria Agrícola, Universidad Autónoma Chapingo, Chapingo, México
  5. 5Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, México
  6. 6Secretaría de Ciencia, Humanidades, Tecnología e Innovación, Centro de Investigaciones Biológicas del Noroeste, La Paz, Baja California Sur, Mexico
  7. 7Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Av. Universidad S/N Col. Chamilpa, Cuernavaca, Mor, México
  8. 8Facultad de Ciencias Químicas, Universidad de Colima, Coquimatlán, Colima, México
  9. 9Secretaría de Ciencia, Humanidades, Tecnología e Innovación, Laboratorio de Biología Sintética, Estructural y Molecular, Centro Universitario de Investigaciones Biomédicas (CUIB), Universidad de Colima, Colima, México
  10. 10Facultad de Ciencias Biológicas y Agropecuarias, Universidad de Colima, Tecomán, Colima, México
  11. 11Secretaría de Ciencia, Humanidades, Tecnología e Innovación, Laboratorio de Biología Sintética, Estructural y Molecular, Facultad de Ingeniería Mecánica y Eléctrica, Universidad de Colima, Coquimatlán, Colima, México
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Abstract

Marine microorganisms are a prolific source of novel polyketide synthases (PKSs) that generate structurally diverse and functional polyketides. Here, we identify a novel type III PKS, ArsMB, from Pontimonas sp. via metagenomic mining of a Baltic Sea microbiome. Heterologous expression of arsMB synthetic gene in an Escherichia coli host that lacks a native type III PKS, combined with a two-step strategy to boost acyl-CoA precursor availability in a glucose-mineral medium, enabled the in vivo synthesis of two cell-associated alkylresorcinols, identified by GC-MS as 5-pentadecyl-1,3-benzenediol (ars1) and 5-tridecyl-1,3-benzenediol (ars2). The product profile is consistent with a tetraketide alkylresorcinol biosynthetic pathway utilizing C16 and C14 acyl starter units, drawn from the host acyl-CoA pool. In agreement, AlphaFold2-based structural modeling predicts a Cys139/His275/Asn308 catalytic triad and a long hydrophobic substrate tunnel compatible with long-chain acyl starter units. E. coli producing the amphipathic cell-associated alkylresorcinols ars1/ars2 exhibited increased resistance to muralytic digestion by endolysins and to hydrogen peroxide. These findings expand the known repertoire of marine-derived type III PKSs and highlight the biotechnological potential of ArsMB-derived alkylresorcinols.

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Cite

BibTeXRIS
BibTeX
@article{lopezgutierrez2026baltic,
  title = {{A Baltic Sea microbiome-derived Type III polyketide synthase produces host-protective alkylresorcinols in E. coli}},
  author = {Susana López-Gutiérrez and Laura A. Espinosa-Barrera and Arianna Soto-Hernández and Holber Zuleta-Prada and Celia Bustos-Brito and César S. Cardona-Félix and José Utrilla and Beatriz Velazquez-Cruz and Yair Cárdenas-Conejo and Jesus Alfredo Araujo-León and Victor Aguilar-Hernández and Juan A. Osuna-Castro and Baldomero Esquivel and Hugo Serrano-Posada and Sara Centeno-Leija},
  journal = {PLOS One},
  year = {2026},
  month = nov,
  doi = {10.1371/journal.pone.0361965},
  url = {https://doi.org/10.1371/journal.pone.0361965},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A Baltic Sea microbiome-derived Type III polyketide synthase produces host-protective alkylresorcinols in E. coli
AU  - Susana López-Gutiérrez
AU  - Laura A. Espinosa-Barrera
AU  - Arianna Soto-Hernández
AU  - Holber Zuleta-Prada
AU  - Celia Bustos-Brito
AU  - César S. Cardona-Félix
AU  - José Utrilla
AU  - Beatriz Velazquez-Cruz
AU  - Yair Cárdenas-Conejo
AU  - Jesus Alfredo Araujo-León
AU  - Victor Aguilar-Hernández
AU  - Juan A. Osuna-Castro
AU  - Baldomero Esquivel
AU  - Hugo Serrano-Posada
AU  - Sara Centeno-Leija
PY  - 2026
DA  - 2026/11/03
JO  - PLOS One
DO  - 10.1371/journal.pone.0361965
UR  - https://doi.org/10.1371/journal.pone.0361965
AB  - Marine microorganisms are a prolific source of novel polyketide synthases (PKSs) that generate structurally diverse and functional polyketides. Here, we identify a novel type III PKS, ArsMB, from Pontimonas sp. via metagenomic mining of a Baltic Sea microbiome. Heterologous expression of arsMB synthetic gene in an Escherichia coli host that lacks a native type III PKS, combined with a two-step strategy to boost acyl-CoA precursor availability in a glucose-mineral medium, enabled the in vivo synthesis of two cell-associated alkylresorcinols, identified by GC-MS as 5-pentadecyl-1,3-benzenediol (ars1) and 5-tridecyl-1,3-benzenediol (ars2). The product profile is consistent with a tetraketide alkylresorcinol biosynthetic pathway utilizing C16 and C14 acyl starter units, drawn from the host acyl-CoA pool. In agreement, AlphaFold2-based structural modeling predicts a Cys139/His275/Asn308 catalytic triad and a long hydrophobic substrate tunnel compatible with long-chain acyl starter units. E. coli producing the amphipathic cell-associated alkylresorcinols ars1/ars2 exhibited increased resistance to muralytic digestion by endolysins and to hydrogen peroxide. These findings expand the known repertoire of marine-derived type III PKSs and highlight the biotechnological potential of ArsMB-derived alkylresorcinols.
SN  - 1932-6203
ER  -